Glaucoma: A Comprehensive Clinical Guide

Introduction

Glaucoma encompasses a heterogeneous group of optic neuropathies characterized by progressive retinal ganglion cell death, optic nerve head cupping, and corresponding visual field deficits. Elevated intraocular pressure (IOP) is the primary modifiable risk factor, but glaucomatous damage may occur at normal pressures (normal-tension glaucoma). As one of the leading causes of irreversible blindness worldwide, early detection and tailored management are essential to preserve vision and quality of life.

Epidemiology

• Global Burden: Estimated 80 million affected individuals in 2020, with 11.2 million bilaterally blind. By 2040, projections exceed 111 million.
• Prevalence by Region: Highest burden in Africa and Asia; underdiagnosis exceeds 50% in most populations.
• Demographics: Prevalence increases sharply after age 40; primary open-angle glaucoma (POAG) predominates in individuals of African descent, while primary angle-closure glaucoma (PACG) is more common in East Asian populations.

Classification

1. Primary Open-Angle Glaucoma (POAG): Chronic, insidious, elevated IOP with open anterior chamber angles on gonioscopy.
2. Primary Angle-Closure Glaucoma (PACG): Narrow or closed angles leading to impaired aqueous outflow; acute, subacute, or chronic presentations.
3. Secondary Glaucomas: From ocular or systemic pathology (e.g., pigment dispersion, pseudoexfoliation, uveitis, neovascularization, steroid-induced).
4. Congenital and Developmental Glaucoma: Onset in infancy or childhood; associated with trabeculodysgenesis.

Pathophysiology

• Aqueous Humor Dynamics: Produced by the ciliary epithelium, flows through the pupil and exits via the trabecular meshwork (conventional) and uveoscleral pathway (unconventional). Elevated resistance at the meshwork raises IOP.
• Optic Nerve Damage: Mechanical compression and impaired axoplasmic flow at the lamina cribrosa; ischemic and excitotoxic injury to retinal ganglion cells.
• Pressure-Independent Factors: Vascular dysregulation, oxidative stress, mitochondrial dysfunction, genetic mutations (MYOC, OPTN, TBK1).

Risk Factors

• Elevated IOP: Strongest modifiable risk factor; each 1 mm Hg increase confers ~10% greater risk.
• Age: Risk doubles each decade after 40.
• Race and Ethnicity: Higher POAG risk in African descent; PACG more prevalent in East Asians.
• Family History: First-degree relatives have 7–10× higher risk.
• Myopia and Central Corneal Thickness: High myopia and thin corneas increase susceptibility.
• Systemic Conditions: Diabetes, hypertension, vasospasm, sleep apnea.

Clinical Presentation

• POAG: Frequently asymptomatic until advanced; peripheral visual field loss progressing centrally.
• PACG:
• Acute: Severe ocular pain, headache, nausea, halos around lights, mid-dilated nonreactive pupil, corneal edema, IOP >40 mm Hg.
• Chronic: Insidious angle closure with gradual field loss.
• Secondary Glaucoma: Signs vary based on etiology (e.g., pigmentary deposition in pigment dispersion syndrome, iris neovascularization in neovascular glaucoma).

Diagnostic Evaluation

1. Tonometry: Goldmann applanation as reference; noncontact and rebound devices for screening.
2. Gonioscopy: Assess angle anatomy, synechiae, pigmentation.
3. Optic Nerve Assessment: Stereoscopic fundus exam for cup-to-disc ratio, rim thinning, disc hemorrhages.
4. Visual Field Testing: Standard automated perimetry; detect early arcuate defects, nasal steps, paracentral scotomas.
5. Imaging: Optical coherence tomography (OCT) of retinal nerve fiber layer and ganglion cell complex for quantitative analysis.
6. Anterior Segment Imaging: Ultrasound biomicroscopy or anterior segment OCT for angle evaluation in PACG.

Management Strategies

Medical Therapy

• First-Line Agents:
• Prostaglandin analogs (latanoprost, bimatoprost): increase uveoscleral outflow.
• Beta blockers (timolol): reduce aqueous production.
• Adjunctive Agents:
• Alpha agonists (brimonidine), carbonic anhydrase inhibitors (dorzolamide), rho kinase inhibitors.
• Fixed-Dose Combinations: Improve adherence by reducing instillations.

Laser Therapy

• Laser Peripheral Iridotomy (LPI): Prophylactic or acute management of angle closure.
• Selective Laser Trabeculoplasty (SLT): Enhances trabecular outflow in open-angle glaucoma; repeatable and minimal tissue damage.

Surgical Interventions

• Trabeculectomy: Gold standard filtration surgery; risk of bleb-related complications.
• Minimally Invasive Glaucoma Surgery (MIGS): Trabecular micro-bypass stents, suprachoroidal shunts—lower risk profile in mild-to-moderate POAG.
• Tube Shunts: Preferred in neovascular glaucoma, uveitic glaucoma, failed trabeculectomy.

Patient Education and Adherence

• Emphasize chronic nature of disease and asymptomatic progression.
• Demonstrate correct eye drop instillation technique and discuss potential side effects.
• Incorporate reminder systems, dosing diaries, or adherence apps.
• Coordinate care with primary providers for systemic risk factors and medication interactions.

Monitoring and Follow-Up

• Target IOP: Individualized based on disease severity; typically 20–30% reduction from baseline.
• Frequency:
• Stable, well-controlled: every 6–12 months.
• Advanced or progressing: every 3–4 months.
• Outcome Measures: IOP, visual fields, optic nerve imaging, adherence assessment.

Prognosis

• Early detection and sustained IOP control slow progression but do not reverse existing damage.
• Lifelong monitoring is required; vision-related quality of life may be preserved with appropriate therapy.

Conclusion

Glaucoma management demands a multidisciplinary approach, combining early diagnosis, personalized target IOP strategies, and patient-centered education. Advancements in pharmacotherapy, laser modalities, and minimally invasive procedures continue to expand therapeutic options, underscoring the importance of individualized care plans to optimize visual outcomes.